A Randomised, Stratified, Open Label, Phase II Pilot Study on the Safety of a Daily, Intermittent, or Weekly Administration of 1, 3 or 10mg/kg of AmBisome® in Antifungal Primary Prophylaxis of High-Risk Patients With Acute Myeloid Leukaemia
18 Years
80 Years
Both
Acute Myeloid Leukemia
Trial Information
A Randomised, Stratified, Open Label, Phase II Pilot Study on the Safety of a Daily, Intermittent, or Weekly Administration of 1, 3 or 10mg/kg of AmBisome® in Antifungal Primary Prophylaxis of High-Risk Patients With Acute Myeloid Leukaemia
Invasive Fungal Infections (IFI)are a significant cause of death in patients with acute
leukaemia who are undergoing chemotherapy. This is despite improvements in antifungal
therapy for the treatment of IFI. The major reason for this is that the current standard
diagnostic tests of culture and biopsy lack the ability to make a diagnosis, either early or
accurately. Thus other strategies such as the use of prophylaxis are needed. Several
antifungal agents have been trialled as prophylaxis but all have disadvantages that limit
their effectiveness.
Liposomal amphotericin B(LAB) is a broad spectrum antifungal agent that kills fungal cells.
When given in high doses intermittently it supersaturates the liver and the overspill into
the bloodstream is absorbed by tissues such as lung, brain and kidneys (i.e. sites where IFI
are likely to occur). This effect has been shown in a number of animal and laboratory
test-tube studies to reduce fungal burden, improve survival and maintain adequate levels of
the drug in between doses. However no intermittent high-dose prophylaxis study has been done
in humans. Thus before we proceed to a randomised controlled clinical trial of the efficacy
of intermittent high-dose LAB compared with another antifungal agent it is necessary to
determine in a phase 2 study which of 2 intermittent dosing LAB regimens (i.e. 3mg/kg three
times a week or 10mg/kg once a week) administered during the neutropenic phase of
induction-consolidation chemotherapy for treatment of acute leukaemia is safest and best
tolerated compared to the standard dosing regimen of 1mg/kg daily of LAB.
Males and females aged >18 years who are undergoing intensive combination chemotherapy for
acute leukaemia will be randomised 1:1:1 to either 1mg/kg daily; 3mg/kg 3 times a week or
10mg/kg once weekly of intravenous liposomal amphotericin B. The 3 arms will be compared for
the safety of the 3 dosing regimens.
Inclusion Criteria:
Patients fulfilling all the following criteria will be eligible:
- Male or female aged >18years;
- Newly diagnosed with acute myeloid leukaemia and undergoing first induction
chemotherapy regimen;
- Expected to have absolute neutrophil counts of <0.5x109/L for at least 2 weeks;
- Normal high resolution chest and sinus CT scan at baseline;
- No signs or symptoms of invasive fungal infections
- No prior diagnosis of proven or probable invasive fungal infection within the last 6
months;
- Females of childbearing potential must be: surgically incapable of pregnancy; or
practicing an acceptable mode of birth control and have a negative pregnancy test
(blood or urine) at baseline;
- Give written informed consent prior to any study-specific procedures;
- Must have the ability and must agree to comply with all study requirements.
Exclusion Criteria:
Patients with any of the following will be ineligible
- Known hypersensitivity to amphotericin B, in particular known history of anaphylactic
reaction to amphotericin B;
- Patients undergoing any transplantation;
- Creatinine clearance <60mL/min/1.72 m2;
- Patients with moderate or severe liver disease as defined by aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the upper limit of
normal (ULN)
- Patients who are unlikely to survive more than one month;
- Patients who have received systemic antifungal therapy within the last 15 days
- Any severe cardiovascular disease ( in particular arrhythmias) which may constitute a
contra-indication to LAB (AmBisome®) administration;
- Any severe diseases other than acute myeloid leukaemia which in the investigator’s
judgement may interfere with study evaluations or affect the patients safety;
- Pregnant or nursing females;
- Patients previously included in this study;
- Patients who have taken an investigational drug in the last 30 days prior to the
inclusion.
- Patients enrolled in a pre-emptive treatment strategy trial
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Outcome Measure:
Safety as defined by the incidence of all adverse events occurring by the completion of each trial prophylaxis course.
Principal Investigator
C. Orla Morrissey, MB, BCh, FRACP
Investigator Role:
Principal Investigator
Investigator Affiliation:
The Alfred Hospital, Level 2 Burnet Institute, Commercial Rd., Melbourne, 3004, Victoria, Australia
Authority:
Australia: Department of Health and Ageing Therapeutic Goods Administration
Study ID:
IN-AU-131-0176
NCT ID:
NCT00451711
Start Date:
May 2007
Completion Date:
October 2009
Related Keywords:
- Acute Myeloid Leukemia
- Prophylaxis
- Liposomal Amphotericin B
- Acute myeloid leukaemia
- Invasive Fungal Infections
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
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